bortezomib combined with pd-1 mab and mfolfirinox for metastatic pancreatic cancer

Conditions: Pancreas Cancer

Summary: this is an single-center, prospective, open-label clinical trial, to explore the safty and efficacy of combination of bortezomib, sindilizumab, and mfolfirinox chemotherapy (oxaliplatin, fluorouracil, irinotecan, leucovorin) in metastatic pancreatic cancer

phase 1 (evaluation of drug tolerance) primary objective: to evaluate the tolerability of bortezomib, pd-1 mab and mfolfirinox in patients with advanced metastatic pancreatic cancer, and to determine the dose of bortezomib in the combination regimen; secondary objectives: to evaluate the immunogenicity characteristics and safety of the combination regimen of bortezomib, pd-1 mab and mfolfirinox in patients with advanced metastatic pancreatic cancer; phase 2 (dose expansion) primary objective: to evaluate the tolerability and efficacy of the combination regimen of bortezomib, pd-1 mab and mfolfirinox in patients with advanced metastatic pancreatic cancer; secondary objective: orr; pfs; os; and to evaluate the immunogenicity and safety of bortezomib, pd-1 mab and mfolfirinox in subjects with advanced metastatic pancreatic cancer; and to explore biomarkers related to combination therapy.

Eligibility criteria:
inclusion criteria: * pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma (pdac). * recurrent disease or metastatic disease (such as liver, peritoneum, lung) evaluated by abdominal contrast-enhanced ct, mri, and chest ct. pet/ct or other imaging examinations would be used if necessary. * never receive any systematic treatment or progression after fisrt line gemcitabine base chemotherapy * ecog score 0 or 1. * serum creatinine level is normal, and serum total bilirubin level is less than 1.5 x uln. * alt and ast are less than 2 x uln. * signed informed consent. exclusion criteria: * history of participation of other clinical trails within 4 weeks * history of autoimmune disease or other condition receiving glucocorticoid treatment * history of receiving chemotherapy within 2 weeks * history of radiotherapy and molecular target therapy within 2 weeks * history if active tuberculosis * history of malignance treatment in the past, excluding basal and cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma * major cardiovascular diseases (including myocardial infarction, unstable angina, congestive heart failure, severe uncontrolled arrhythmia) during the past six months of enrollment. * hematological precancerous diseases, such as myelodysplastic syndromes. * evidence of clinical-related or previous interstitial lung disease, such as noninfectious pneumonia or pulmonary fibrosis, or baseline chest ct scan or chest x-ray findings * previous or physical findings of central nervous system disease, except for adequately treated (e.g. primary brain tumors, uncontrolled seizures or strokes with standard medications) * preexisting neuropathy \> 1 (nci ctcae). * immune deficiency syndrome, such as active tuberculosis and hiv infection. * allograft requires immunosuppressive therapy or other major immunosuppressive therapies. * severe serious wounds, ulcers or fractures. * clinical evaluation is unacceptable

Keywords: metastatic pancreatic cancer bortezomib pd-1 antibody chemotherapy